A bacterium is gram-positive if it resists decolorization by alcohol after
the application of a primary stain. The gram-positive bacteria as
a class form a much tighter phylogenic cluster than do the gram-negative
bacteria. The gram-positive cocci consist of genera that are somewhat
diverse but grouped together for convenience because of the spherical
shape of their cells and their gram-positive staining. They do not
form endospores; motility is uncommon. The genera fall into reasonably
distinct categories of aerobic, facultatively anaerobic, and strictly
anaerobic genera (Table 1). The arrangement of the cells and the occurrence of catalase are important
distinguishing methods.

The backbone of a bacterial cell wall is peptidoglycan, which is composed
of layers of polysaccharide chains that are linked by short peptides. The
alternating sugars in the peptidoglycan are N-acetylmuramic acid
and N-acetylglucosamine. The peptidoglycan has important biologic properties: it
elicits the production of interleukin-1 from human monocytes, induces
a local Swartzmann reaction, is capable of attracting polymorphonuclear
neutrophils (PMNs), has endotoxin-like activity, activates
complement, and elicits the production of opsonic antibodies.1 The cell wall of gram-positive bacteria is very thick compared with the
gramnegative peptidoglycan layer and consists of layer upon layer of
molecules, accounting for 50% to 60% of the total dry weight of the cell
wall. Much of the remaining cell wall material is a special polysaccharide
called teichoic acid, which is interwoven in the peptidoglycan
matrix permeating the cell wall and appearing on the surface of the
organism. Some of the teichoic acids have a lipid attached (lipoteichoic
acid), which is embedded in the cytoplasmic membrane. Different strains
and species of gram-positive bacteria differ in teichoic acid structure
and in surface proteins.

The cross-linking of polysaccharide chains by way of peptides results in
a very rigid cell wall. The cell wall protects the organism from lysis
under harsh osmotic conditions and aids in attachment of the bacteria
to mucosal cell receptor sites. Many Staphylococcus aureus strains and other grampositive bacteria are coated with an external polysaccharide
capsule that can be released during focal infection.2

Gram-positive cocci of ophthalmic importance are members of the genera Staphylococcus, Streptococcus, and Enterococcus. Because most infections are acute and associated with a chemoattraction
for PMNs, the pathogenic cocci are often referred to as pyogenic cocci.

Members of the genera Staphylococcus and Micrococcus are catalase-positive, gram-positive bacteria and are placed with Stomatococcus and Planococcus in the family Micrococcaceae. The family is not phylogenically coherent
based on DNA composition, RNA hybridization, and comparative oligonucleotide
cataloging of RNA.3 The genus Staphylococcus is composed of 32 species, and the genus Micrococcus is composed of 9 species. Serologic tests have limited usefulness in identifying
staphylococci. Phage typing is performed only in reference
laboratories for epidemiologic studies.

Members of the genus Staphylococcus occur singly, in pairs, or in grapelike clusters. They are nonmotile, are
non-spore-forming, and are usually unencapsulated or have limited
capsule formation. Most are facultative anaerobes with more rapid and
abundant growth under aerobic conditions. They are among the hardiest
non-spore-forming bacteria, and they can survive many nonphysiologic environmental
conditions. Staphylococci are widespread in nature, with
heavy concentration on the skin, skin glands, and mucous membranes. Staphylococci
are ubiquitous human parasites, and their chief sources of
infection include shedding human lesions, fomites contaminated from such
lesions, and from the human respiratory tract and skin. Many neonates, and
most children and adults, will become intermittently colonized
by Staphylococcus aureus. Contact spread of infection has assumed added importance in hospitals, where
a large proportion of the staff and patients carry antibiotic-resistant
staphylococci in the nose or on the skin. Physicians, nurses, and
hospital ward attendants may be nasopharyngeal carriers in a higher
percentage of cases (50%, 70%, and 90%, respectively) than the general
population (33%).4 Approximately 20% of adults are chronically colonized, and another 10% to 20% are
transiently colonized at a given time. These rates are even
higher for drug users and patients with chronic skin diseases or renal
disease requiring hemodialysis.5 This carrier state can serve as a reservoir for the infection of hospitalized
patients, although most carriers do not disseminate the organism
and are not a risk to others. In hospitals, the areas at highest risk
for severe staphylococci infections are the newborn nursery, intensive
care units, operating rooms, and cancer chemotherapy wards.

The increased use of intravenous access devices and invasive procedures
has been a factor in the changing spectrum of Staphylococcus aureus infections.6 Infection occurs when bacteria colonize the skin around the catheter entry
site, propagate along the track of the catheter, and enter the vascular
compartment. Attachment of Staphylococcus aureus to traumatized or disrupted skin, to foreign surfaces, and to endothelial
structures involves interaction with at least five different proteins (fibrinogen, fibronectin, laminin, thrombospondin, and possibly collagen
IV). Staphylococci species found most often as pathogens include Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus haemolyticus.

The coagulase-positive species, Staphylococcus aureus, is a significant opportunistic pathogen with major morbidity and mortality
as a nosocomial organism.7,8 All other human species are collectively referred to as the coagulase-negative
staphylococci. The capsule is a cell wall surface structure that
is well documented as a virulence factor for staphylococci. Certain
strains of Staphylococcus aureus produce a polysaccharide capsule that helps to protect it from phagocytosis
by PMNs. The mechanism by which the capsule mediates resistance
to phagocytosis appears to involve interference with recognition of the
opsonins that bind to the cell wall underneath the capsule by rendering
the opsonins inaccessible for recognition by phagocytic cells. Staphylococcus aureus incorporates covalently into its outer peptidoglycan layer a protein with
a molecular weight of 42,000 d, protein A, which binds to the Fc terminal
of all human immunoglobulin G subclasses except IgG3. Protein
A prevents antibody-mediated phagocytosis by PMNs. In the bloodstream, aggregates
of IgG bound to protein A on staphylococcal surfaces will
fix complement, causing complement-mediated tissue damage to the host.

The initial stage in infection is adherence to the host, which is accomplished
by specific interaction of the staphylococcal adhesin (lipoteichoic
acid) with the host epithelial cell receptor (fibronectin).5Staphylococcus aureus produces a number of enzymes and toxins that, along with the invasive
properties of the strain, contribute to its pathophysiology. The prototype
of a staphylococcal lesion is a focal abscess with some of the disease
patterns associated with toxin production. Staphylococcus aureus produces the enzymes catalase, coagulase, phosphatase, thermostable deoxyribonuclease
and ribonuclease, lipase, gelatinase, protease, and fibrolysin (Table 2). Catalase production differentiates staphylococci from streptococci. Coagulase
coats the surface of staphylococci with fibrin and may prevent
phagocytosis. It also circumvents the normal plasma clotting cascade. Hyaluronidase
may facilitate spread of infection through the tissues. The
alpha, beta, gamma, and delta toxins act on red and white blood
cell and platelet membranes of some species and on sphingomyelin, vascular
smooth muscle, or other membranes. Many Staphylococcus aureus strains produce a leukocidin that increases the permeability of leukocytes
to cations and subsequently leads to swelling and rounding up of
the cells; the membranes of cytoplasmic granules fuse with the cytoplasmic
membrane of the cell, causing release of the cytoplasmic granules
and cell disruption. The rigid cell wall elicits production of interleukin-1 and
opsonic antibodies by monocytes. It can be a chemoattractant
for polymorphonuclear leukocytes, have an endotoxin-like activity, produce
a localized Swartzmann phenomenon, and activate complement.

TABLE 2. Toxins and Enzymes of Gram-Positive Organisms

Staphylocci

Streptococci

Enterococci

Catalase

Streptokinase

Cytolysin

Coagulase

Streptodornase

Hyaluronidase

Hyaluronidase

Staphylokinase

Deoxyribonuclease

Proteases

Proteases

Phosphatase

Neuraminidase

Deoxyribonuclease

Pyrogenic exotoxins

Ribonuclease

Pneumolysin

Fibrinolysin

Diphosphopyridine nucleotides

Gelatinase

Clumping factor

Streptolysins (hemolysins)

Lipases

Cardiohepatic toxin and nephrotoxin

β-lactamase

Exotoxins

Spreading factors

Alpha toxins

Beta toxins

Gamma toxins

Delta toxins

Leukocidin

Exfoliative toxin (exfoliatin)

Toxic shock syndrome toxin

Enterotoxins

Lysozyme is secreted by some strains of staphylococci, primarily coagulase-positive
strains. It has the ability to lyse certain bacteria by acting
as a muramidase to cleave portions of the bacterial cell wall, especially
micrococci. It may digest debris from cell walls of bacteria
killed in other ways and thereby facilitate clearing of debris from clinical
lesions.

Other important toxins of Staphylococcus aureus include enterotoxins, exfoliative toxins, and the toxins associated with
toxic shock syndrome. These are all included within a recognized class
of immune system modulators, the superantigens. These superantigens
bind major histocompatibility complex II molecules, stimulating T cells
independently of other mediators, and subsequently cause systemic
effects, including the release of cytokines such as interleukin-2, gamma
interferon, and tumor necrosis factors.9Staphylococcus aureus produces at least six different enterotoxins, some of which are implicated
in food poisoning and antibiotic-induced pseudomembranous colitis. The
exfoliative toxin causes the staphylococcal scalded skin syndrome, which
cleaves the middle layers of the epidermis, allowing the surface
skin to peel.

Food poisoning is often attributed to staphylococcal enterotoxin, although
the bacterium is usually not isolated from the patient. A community-acquired
disease of potentially serious consequence, toxic shock syndrome, has
also been attributed to infection or colonization with Staphylococcus aureus. This is associated with strains that secrete a specific superantigen
exotoxin that stimulates T cells and is also a potent inducer of tumor
necrosis factor and the cytokine interleukin-1.3 This is a systemic disease characterized by fever, hypotension, and multiorgan
involvement but negative blood cultures.10 Although most cases have occurred in menstruating young females who are
vaginal carriers of Staphylococcus aureus, other sites, including abscesses or wounds, may harbor the toxinproducing
organisms.

Staphylococcus aureus infections are often acute and pyogenic with spread to surrounding tissues
or to metastatic sites by means of a bacteremia. Some of the skin
infections caused by Staphylococcus aureus include furuncles, cellulitis, impetigo, scalded skin syndrome, and postoperative
wound infections. Other major infections caused by Staphylococcus aureus include bacteremia, pneumonia, osteomyelitis, acute endocarditis, myocarditis, pericarditis, cervicitis, cerebritis, meningitis, and abscesses
of the muscle, urogenital tract, central nervous system, and various
intra-abdominal organs (Table 3).

The coagulase-negative Staphylococcus species constitute a major component of the normal microflora in humans. Although
the coagulase-negative staphylococci do not produce the number
of extracellular products that Staphylococcus aureus does, many species produce hemolysins, and some may possess an antiphagocytic
capsule. It is occasionally important to identify the individual
species of coagulase-negative staphylococci involved in an infection
because of clinical, economical, and therapeutic implications; laboratory
tests have been developed to differentiate among these staphylococci.

Infection with Staphylococcus epidermidis has been increasing. This increase correlates with the use of prosthetic
and indwelling devices and the growing number of immunocompromised
patients in hospitals.11,12Staphylococcus epidermidis has been isolated from hospital-acquired bacteremia, osteomyelitis cardiac
valve and cardiotomy infections, cerebrovascular fluid shunts, prosthetic
joints, and orthopedic devices. It also has been isolated during
ambulatory peritoneal dialysis. Staphylococcus saprophyticus is an opportunistic pathogen in human urinary tract infections and in
urethritis. Staphylococcus haemolyticus also has been associated with a variety of clinical infections, many with
underlying immune diseases or intravascular manipulations. Because
the coagulase-negative bacteria are a major cause of foreign-body infections, there
may be a polysaccharide adhesion to biomaterials that initiates
a biofilm formation.11 The production of a biofilm can mediate bacterial adherence and correlates
with pathogenicity.13 The slime inhibits the polymorphonuclear cell response to chemotactic
substances and stimulates these cells to degranulate, thus reducing the
uptake and killing of bacteria.

Micrococci occur mostly in pairs or clusters and are obligate aerobes. Distinction
is made between staphylococcus and micrococcus based on DNA, cell
wall differences, and a host of clinical laboratory tests.3 Micrococcus also is found in the same locations as staphylococci, but
they are much less virulent than the staphylococci. The predominant species
found in humans includes M. luteus, M. roseus and M. varians.3 Micrococci are saprophytes that colonize the skin, mucosa, and oropharynx. They
can be opportunistic pathogens in immunocompromised patients. M. luteus has been implicated as the causative agent in intracranial abscesses, septic
arthritis, endocarditis, and meningitis.

Species of stomatococcus have been recovered from compromised patients, particularly drug abusers, as
the cause of endocarditis and septicemia.14 They are known as “sticky staph” because their capsules can
adhere to the agar.

Streptococci are catalase-negative, gram-positive facultative anaerobic
bacteria that are spherical or ovoid in shape and less than 2 μm in
diameter. They are a heterogeneous group of bacteria characterized by
a combination of features, such as colony growth characteristics, hemolysis
patterns on blood agar, antigenic composition of group-specific
cell wall substances, biochemical reactions, and antigenic composition
of capsular polysaccharide. No one system classifys them. Recently
the taxonomy of streptococci changed: the enterococci (previously considered
group D streptococcus) and the lactococci (previously considered
group N streptococci) now reside in their own genera, Enterococcus and Lactococcus, respectively. As a first step in identifying clinical isolates, the traditional
phenotypic criteria (hemolytic reactions and Lancefield serology) for
classification can still be used to divide the streptococci
into broad categories.

Lancefield and co-workers developed a technique for differentiating the
streptococci based on serologic groups A through O on the basis of the
antigenic characteristics of a cell-wall carbohydrate called the C substance. More
than 90% of streptococcal disease in humans is caused by
Group A β-hemolytic streptococci. These β-hemolytic isolates
with Lancefield group A, C, or G antigen can be subdivided into two
groups: large-colony and small-colony formers. Large-colony forming group
A (Streptococcus pyogenes), C, and G strains are “pyogenic” streptococci replete with
a variety of effective virulence mechanisms.15,16 The smallcolony forming β-hemolytic strains are members of the Streptococcus milleri group that are usually much less pathogenic.17 Among the non-β-hemolytic streptococcal strains, alpha-reacting isolates
can be separated into Streptococcus pneumoniae and the viridans division, which is composed of a number of species groups. The
nutritionally variant streptococci, previously thought to be
nutritional mutants of viridans strains, have been shown to constitute
a separate group of streptococcal species.18 Organisms previously thought to be anaerobic streptococci have been shown
to be unrelated to members of the genus Streptococcus.19

Streptococci are usually found as parasites of humans. Some streptococci
function as virulent pathogens while other strains live as avirulent
commensals. Streptococci colonize the skin and mucous membranes, and
they can be isolated as part of the normal flora of the alimentary, respiratory, and
genital tract.

The β-hemolytic Lancefield Group A streptococci (Streptococcus pyogenes) are significant pathogens related to numerous virulence factors. These
factors include M protein, lipoteichoic acid, enzymes, and toxins that
allow it to cause a wide array of serious infections (e.g., pharyngitis, respiratory infection, skin and soft tissue infections [impetigo, erysipelas], endocarditis, meningitis, puerperal sepsis, and
arthritis).15 Toxin-producing strains can cause scarlet fever or toxic shock-like syndromes. Sequelae
of pharyngitis can include spread to contiguous tissue
or bacteremia. Streptococcus pyogenes produces various extracellular products and toxins that enhance virulence. Erythrogenic
toxin, elaborated by scarlet fever-associated strains, is
responsible for the characteristic rash. Group A streptococci produce
deoxyribonuclease, hyaluronidase, streptokinase, NADase, and proteinases. Streptokinase
is a fibrinolysin that transforms plasminogen
into plasmin and digests fibrin. It is used pharmacologically to dissolve
emboli and thromboses. Streptodornase depolymerizes DNA and is used
pharmacologically for enzymatic debridement. Hyaluronidase splits hyaluronic
acid and elicits specific antibodies in the serum. The two hemolysins, streptolysin
O and streptolysin S, can lyse human and other
erythrocytes, as well as the cell membranes of polymorphonuclear cells, platelets, and
other cells. Antistreptolysin O serum titer suggests
recent infection. It is also implicated in the pathogenesis of rheumatic
fever. Three potent pyrogenic exotoxins can induce fever and encourage
development of acute respiratory distress syndrome, renal failure, and
tissue necrosis.16 They can cause an erythrogenic rash and toxic shock. In primary streptococcal
infections the infecting strain is often capable of spreading
to surrounding tissue because of various extracellular products, including
hyaluronidase, proteinase, streptokinase, and nucleases.

The streptococcal cell wall contains proteins (M, T, and R antigens), carbohydrates (group-specific), and peptidoglycans. M protein is a filamentous
macromolecule that exists as a stable dimer with an alpha-helical
coiled structure; it is anchored to the cell membrane, traverses, and
then penetrates the cell wall. Hairlike pili project through the capsule
of group A streptococci. The pili consist partly of M protein and
are covered by lipoteichoic acid. The cell wall lipoteichoic acids
serve to effect adherence of the organism to host cell respiratory epithelium, which
is an essential initial step that is necessary for the
start of infection. The M protein is the major virulence factor of the
bacteria; some of the streptococcal pyrogenic exotoxins and some M antigens
can act as activators of T-cells and systemic immunomodulators. The
T protein provides a system of serotyping strains that cannot be
typed by their M protein. T protein is often used for identification of
streptococcal strains isolated from patients with impetigo. Both the
hyaluronic acid capsule and cell wall M protein serve to prevent phagocytosis. Mucoid
strains possess a large hyaluronic acid capsule that
acts to inhibit phagocytosis.

Nonsuppurative sequelae of streptococcal infection include rheumatic fever
and acute glomerulonephritis. Although the pathogenesis of these nonsuppurative
diseases is not entirely clarified, they are probably autoimmune
phenomena with cross-reactive antibodies originally directed
against streptococcal cell membranes (C substance) binding to myosin in
human heart muscle cells and other cross-reactive antibodies binding
to components of the glomerular basement membrane. An alternative view
is that these conditions are caused by streptococcal toxins acting as
superantigens due to release of immune cytokines.20 Acute rheumatic fever occurs only after upper respiratory tract infection
dependent on host factors, such as histocompatibility-linked antigen
type, immunoglobin secretory status, and immune responsiveness and
factors of the organism (e.g., adherence mechanisms and cell wall carbohydrate components). Glomerulonephritis
occurs after pharyngitis or after suppurative skin infection
caused by a limited number of serotypes. These serotypes are defined
by the existence of antisera against the M protein component of the cell
wall. A recent upsurge in serious invasive group A streptococcal disease
is a public health concern.16 This disease can strike otherwise healthy adults with minimal focus of
disease and can be community acquired; nearly half the patients may die.

β-Hemolytic streptococci with Lancefield Group B antigen (Streptococcus agalactiae) are a frequent cause of serious neonatal infection characterized by sepsis
and meningitis in up to 3.7 per 1000 live births.21 Their normal carriage site is in the oral cavity, intestinal tract, or
vagina. The colonization of group B streptococci in pregnant women usually
occurs through the gastrointestinal tract. In immunosuppressed patients, it
is associated with endocarditis, pneumonia, and pyelonephritis; in
others, it is associated with joint infection, osteomyelitis, and
wound infection.

Other β-hemolytic streptococci that are not Group A or B usually belong
to Group C or G; they cause a wide range of rare but serious infections
such as bacteremia, endocarditis, meningitis, septic arthritis, as
well as infections of the respiratory tract and skin. Other small β-hemolytic
strains may be nongroupable and are usually identified
as Streptococcus milleri. These organisms are usually commensal, but they can be involved in urogenital
tract infections, abscesses, and other purulent soft tissue infections.

Streptococcus pneumoniae is an important agent of community-acquired pneumonia that may be accompanied
by bacteremia.22 This diplococcus is a common inhabitant of the oropharynx and makes interpretation
of expectorated sputum difficult. It is an exclusively human
pathogen, spread from person to person by aerosols. Other pneumococcal
infections include otitis media, sinusitis, meningitis, and endocarditis. The
pneumococci are facultative anaerobes and are fastidious
in their cultural requirements. The organisms are surrounded by an antiphagocytic
capsule composed of polysaccharide antigens that are useful
in strain typing (more than 80 types are described). The capsular polysaccharide
is the primary virulence factor, but the pathogenesis of
serious infection is related to the inflammatory responses to pneumococcal
cell wall components (teichoic acid and peptidoglycan) and other
proteins. Pneumococci cause disease in the presence of predisposing host
conditions, often a preceding viral respiratory tract infection. The
capsular polysaccharide plays a key role in allowing the establishment
of infection by resisting phagocytosis; antibody to the capsular antigen
is protective against pneumonia. Streptococcus pneumoniae produces several other factors that may play a role in virulence, including
pneumolysin O, an oxygen-sensitive toxin that is cytolytic for cells, and
neuraminidase, an enzyme that degrades surface structures of
host tissue. The cell walls of pneumococci contain C substance, a teichoic
acid that reacts with a certain serum protein, resulting in the
activation of some nonspecific host immune responses.

The viridans species of Streptococcus is derived from the Latin word “viridis,” meaning “green,” because
many members of this group are α-hemolytic and
produce a “green” discoloration in blood agar.23 Strains of viridans streptococci are normal inhabitants of the oral cavity, gastrointestinal
tract, and female genital tract. They do not react
with Lancefield grouping sera. They are not usually primary pathogens
but act as opportunistic challengers to the host. Viridans streptococci
are considered to be bacteria of low virulence because they possess
no endotoxin and secrete little exotoxins. They are frequent contaminants
in blood cultures and have also been associated with subacute
bacterial endocarditis, especially in patients with damaged or prosthetic
valves. They can also be pathogens in neutropenic patients. The amount
of dextran produced by a streptococcal strain correlates with its
ability to adhere to cardiac valves. These strains are also associated
with brain abscess, perioral abscess, aspiration, liver abscess, and
other suppurative infections, often in combination with other bacterial
species or anaerobes. There are seven species: Streptococcus anginosus, Streptococcus bovis variants, Streptococcus mitis, Streptococcus mutans, Streptococcus salivarius, Streptococcus
sanguis, and Streptococcus vestibularis. Some species of viridans streptococci produce extracellular enzymes and
toxins similar to those produced by β-hemolytic streptococci. Gingival
disease and dental manipulations, including dental prophylaxis, are
often predisposing factors in the development of endocarditis. Streptococcus mutans has been definitively established as a major cause of dental carries and
is also a cause of endocarditis. Extracellular polysaccharides, called
dextrans, serve as attachment mediators for tooth surfaces as well
as heart valves.

Streptococcus bovis, a group D streptococcus, can be associated with malignancies of the gastrointestinal
tract, endocarditis, or meningitis. The presence of Streptococcus bovis bacteremia, with or without endocarditis, is almost always indicative
of a loss of integrity of the gastrointestinal mucosa and frequently indicates
a colon malignancy.24

The nutritionally variant streptococci are normal residents of the oral
cavity but have been identified as agents of endocarditis as well as
ophthalmic infections.25 There are two separate species, Streptococcus defectivus and Streptococcus adjacens.18 Nutritionally variant streptococci require vitamin B6, or pyridoxal, for growth on agar. Staphylococcus aureus can provide the necessary growth factors for development of satelliting
colonies of the streptococci in a zone surrounding the staphylococcus. The
exact taxonomic relationship between nutritionally variant streptococci
and viridans streptococci is uncertain.

Peptostreptococcus consists of many species that grow only under anaerobic or microaerophilic
conditions. Most are nonhemolytic. They are part of the normal flora
of the mouth, upper respiratory tract, bowel, and female genital tract. They
often participate with many other bacterial species in mixed
anaerobic infections in the abdomen, pelvis, lung, or brain. These anaerobic
cocci are phylogenically distinct and are covered in a separate
chapter.

The enterococci occur singly or in short chains and are sometimes coccobacillary. They
are facultatively anaerobic. Clinical isolates are catalase
negative. Genetic evidence by DNA and RNA studies has concluded
that the genus Enterococcus is valid with 19 species presently identified, the most important being Enterococcus faecalis and Enterococcus faecium. Enterococci possess group D teichoic acid antigen.

Enterococci are ubiquitous in nature, surviving under harsh conditions, and
this makes establishing clinical significance difficult. There is
an increasing trend in their clinical significance.26 Enterococci are the second or third most common etiologic agents of nosocomial
infection in the Unites States, especially in association with
medical devices. Enterococci are often involved in urinary tract infections, usually
in patients with structural abnormalities. Intra-abdominal
or pelvic wound infections are commonly encountered,27 as is bacteremia caused by this organism. Enterococci are estimated to
cause between 5% and 20% of bacterial endocarditis cases, with E. faecalis being the most commonly encountered enterococcus.26 Surperinfection with enterococci, including bacteremia, is a relatively
common occurrence in patients being treated with a third-generation
cephalosporin because they are resistant to these agents as well as to
penicillin.

Host factors that favor the spread of gram-positive infections in the eye
are similar to factors involved elsewhere. Local immunosuppression, diabetes, and
the use of implants are the most important factors. Interference
with the tear film and damage to the cornea through the use
of contact lenses are local predisposing concerns. The production of multiple
toxins enhances the virulence of these organisms. Some of the
reactions are immunologic events, such as peripheral corneal infiltrates, infectious
eczematoid dermatitis, and phlyctenules related to staphylococci
and uveitis related to streptococci.

In general, staphylococci produce localized abscesses. Staphylococci are
also the most common secondary invaders in many conditions, including
dacryocystitis, trachoma, pemphigus, keratomalacia, and viral superinfections. Both Staphylococcus aureus and Staphylococcus epidermidis are a frequent cause of nosocomial infections. These two organisms are
responsible for infections with implanted medical devices28 correlated with the specific polysaccharide intercellular adhesin production
by some strains29 of Staphylococcus epidermidis and by the fibronectin-binding protein adhesins of Staphylococcus aureus.30,31Staphylococcus epidermidis has the ability to produce a biofilm slime, which promotes the colonization
of smooth surfaces.32 Dextran production in oral streptococci has been shown to correlate with
both the capacity to produce dental caries and the ability to cause
bacterial endocarditis.33

Streptococci can produce a number of severe serious diseases with invasive
spreading properties that are correlated with the secretion of a number
of toxins and enzymes. The pyogenic process for streptococci appears
in the form of a cellulitis rather than as the localized abscess
typical of staphylococcal infections. Streptococcus pneumoniae causes serious ocular infection by invasiveness and multiplication but
does not produce significant toxins. Because Streptococcus pneumoniae or other gram-positive organisms are often present in the normal flora, any
ocular injury may lead to severe purulent infection. The characteristic
pathology of pneumococcal infections is marked edema and fibrinous
exudate, often with an explosive onset. The membrane-active toxins
alpha of Staphylococcus aureus34 and pneumolysin of Streptococcus pneumoniae35 contribute to the virulence of each of these bacteria for corneal disease
and probably endophthalmitis. The toxin cytolysin produced by E. faecalis has been shown to be responsible for the severe destructive endophthalmitis
characteristic of this organism.36

Many gram-positive bacteria display several adhesins on fimbriae (pili) and
nonfimbriated structures that recognize carbohydrates on host cells
or alternatively enhance protein-protein interactions. The adherence
of Staphylococcus aureus, Streptococcus pneumoniae, and Pseudomonas aeruginosa to injured corneal epithelium is significantly higher than that in other
bacteria.37 The degree of binding also depends on epithelial cell factors, as evidenced
by the greater affinity of Staphylococcus aureus to the nasal mucosa of carriers compared with noncarriers. The presence
of M protein or lipoteichoic acid in Streptococcus pyogenes correlates with increased adherence to epithelial cells. In the cornea, damaged
epithelium is particularly susceptible to bacterial adherence, and
it is the epithelial edge rather than the bare stroma to which
bacteria adhere. Exopolysaccharide formation by some organisms results
in local immunosuppressive effects, interfering with phagocytosis. The
bacterial exotoxins can cause severe stromal destruction. Coagulase-positive
strains of staphylococci are the most pathogenic and elaborate
other extracellular enzymes, such as staphylokinase, lipase, hyaluronidase, DNAase, coagulase, and lysozyme. Staphylococcus epidermidis also produces a potentially destructive toxin to the cornea.38 Other virulence factors produced by Staphylococcus aureus and Staphylococcus epidermidis include lipoteichoic acid as well as other components of their capsule. Streptococcal
toxins include streptolysin O and S, erythrogenic toxin, and
the enzymes hyaluronidase, streptodornase, streptokinase, and collagenase. Pneumococci
can proliferate in the presence of neutrophils
because peptidoglycan and M protein inhibit opsonization, impair complement
activation, and reduce leukocyte migration.

Antibiotic resistance, especially to the grampositive cocci, is an emerging
clinical problem. Most Staphylococcus aureus are resistant to penicillin, and multidrug resistance is now quite common. Forty
percent of nosocomial infection cases in the United States
are caused by methicillin-resistant Staphylococcus aureus. Sixty percent of coagulase-negative staphylococci are methicillin resistant. Penicillin-resistant Streptococcus pneumoniae represents 40% of Streptococcus pneumoniae in some communities, with many multiresistant. Vancomycin-resistant Enterococcus represents 16% of enterococci in intensive care units, and many are also
resistant to newer agents, including teicoplanin. Fluoroquinolone resistance
is increasing among streptococci, enterococci, and staphylococci.

Many of these antibiotic resistance problems are related to excessive, inappropriate, and
extended antimicrobial prescribing patterns that have
led to the emergence of resistance. The failure to use basic infection
control measures has increased the dissemination of resistant strains
in hospitals. National guidelines for antibiotic use have not worked
because medicine is practiced according to local standards and is not
nationally driven. Hospital leadership is necessary to combat this
trend by enforcing and policing the recommendations of infectious disease
experts. Strategic goals and processes have the potential to slow
down antibiotic resistance patterns.

SKIN DISEASE

Folliculitis can be divided by its clinical manifestations into superficial
and deep staphylococcal infections. The superficial form, called
Bockhart's impetigo, is common in children, whereas the deep form, called
sycosis barbae, is seen almost exclusively in men. In Bockhart's
impetigo, the focal or clustered lesions are small superficial
follicular pustules that are yellowish in color and have a thin rim
of erythema. Common locations for these lesions are the scalp, back, and
extremities. Sycosis barbae is characterized by pustules, papules, and
nodules in the beard area.

Crusted impetigo is a pustule that ruptures to a thickly crusted dermatitis
of exposed skin areas. It usually occurs in children and has a tendency
to develop in endemic foci during the warm, humid summer months. Amber
serous fluid exudes from the erosion. Impetigo may develop secondarily
around pre-existing varicella or herpes simplex lesions of the
eyelids. This infection is caused by Streptococcus pyogenes, Staphylococcus aureus, or both, so therapy must address both organisms. The vesicopustule is
under the corium and contains numerous neutrophils and a few acantholytic
cells and gram-positive cocci. The upper dermis is involved with a
moderately dense mixed-cell infiltrate.

Bullous impetigo is a localized form of the staphylococcal scalded skin
syndrome. It is characterized by fragile, flaccid bullae that can rupture
to form thinly crusted lesions. The bulla fluid can be clear or cloudy
and up to 3 cm in diameter. Regional lymphadenopathy is uncommon. It
is an endemic disease with a propensity to occur in epidemics, especially
in neonates or children, and is less common than impetigo. It
represents a localized form of Staphylococcus aureus infection with the focal effect of an epidermolytic toxin. Rarely, Streptococcus pyogenes causes a similar process.39 The toxin disrupts intercellular attachments of cells in the granular
layer of human epidermis.40 The cleavage plane for the bulla lies in the subcorneal or granular region. There
is a mixed perivascular and interstitial infiltrate in the
upper dermis.

Ecthyma is characterized by an ulceration of the skin covered by a dirty-appearing
crust. The ulcers are painful and chronic. They occur commonly
on the lower extremities and were seen in American infantrymen in
Vietnam. They very rarely involve the lids or periorbita. The initial
lesion is a vesicle with an erythematous base that erodes through the
epidermis to form a shallow dermal ulcer.41 The ulcer enlarges over several days with a margin that is indurated, raised, and
erythematous. Histopathology reveals an ulcer with nonspecific
features and numerous neutrophils both in the dermis and in the serous
exudate on the ulcer floor. It is primarily an Streptococcus pyogenes infection with secondary Staphylococcus aureus colonization. Ecthyma heals with scarring that can lead to significant
lid deformities.

Erysipelas (St. Anthony's fire) is a distinctive streptococcal infection
of the dermis with prominent lymphatic involvement. It presents
as a painful, red, spreading, hot plaque that is sharply demarcated from
surrounding skin. The lids may be dramatically swollen. This form
of infection can invade the soft tissues of the orbit, resulting in chemosis, mild
proptosis, and limitation of ocular movement.42,43 The surface may be covered by small vesicles or pustules. Systemic symptoms
of fever and chills can occur for days before the dermatitis is
visible. It most commonly occurs on the face or legs. Diabetes and alcohol
abuse are common associations.44 Some cases have no apparent portal of entry of the organism. Tender preauricular
lymph nodes are present, and the lymph tissue may be a source
of spread. Streptococcus pyogenes is the most common etiologic agent, although it is cultured only 40% of
the time. Combining culture, direct immunofluorescence, and serologic
studies increases the evidence for a streptococcal etiology.45 Blood cultures are positive in less than 10% of cases.44 Complications of the acute infection include septicemia, abscesses, necrotizing
fasciitis, and cavernous sinus thrombosis. The papillary dermis
shows prominent edema, which may progress to subepithelial blister
formation. Lymphatics and capillaries are dilated. There is a sparse
infiltrate of predominantly neutrophils throughout the dermis.

Preseptal cellulitis can progress to necrotizing fasciitis, gas gangrene
of the subcutaneous tissue, vascular thrombosis, and necrosis of the
overlying eyelid skin. There may be necrosis (gangrene) of the preseptal
and tarsal skin, with eschar formation and purulent discharge. The
most common pathogens are group A streptococci, although Haemophilus influenzae, P. aeruginosa, and Clostridium species have been involved. Several reports suggest that the incidence
of invasive group A streptococcal infections, including toxic shock syndrome
and necrotizing fasciitis, is increasing.46 Although initial reports found healthy young adults at increased risk, more
recently identified risk factors include HIV infection, cancer, diabetes, alcohol
abuse, and chickenpox46; the mortality rate is 15% overall. There is a shift to a greater frequency
of M serotypes associated with greater virulence.47 There is a substantial risk of transmission in households and health care
institutions, although the precise mode of transmission remains unknown.

Cellulitis is an infectious and inflammatory condition of the skin and
subcutaneous tissues. Because both the dermis and the subcutis are involved, the
sharply defined margin of erysipelas is not present, but erythema, heat, swelling, induration, and tenderness are still present. Cellulitis
occurs most commonly on the legs, but approximately 10% of
cases occur on the face.48 The disease affects predominantly men. The bacterial etiology has been
difficult to establish, but combined culture, direct immunofluorescence, and
serologic studies are most commonly positive for Streptococcus pyogenes in extremity cellulitis.45 The facial involvement is usually a disease of childhood, with additional
involvement of H. influenzae or Streptococcus pneumoniae.40 Preseptal cellulitis presents with periorbital swelling, eyelid edema, erythema, and
localized tenderness but without orbital involvement. It
can occur after localized trauma, insect bites, impetigo, erysipelas, or
acute hordeolum, or by arterial and venous communications from otitis
and paranasal sinus infections. Post-traumatic preseptal cellulitis
occurs after puncture wounds, lacerations, or blunt trauma, with the
main pathogens being Staphylococcus aureus and Streptococcus pyogenes. In young children, H. influenzae type b and Streptococcus pneumoniae are the most common causes of preseptal cellulitis without antecedent
skin infection or trauma and are thought to spread from the upper respiratory
tract, sinuses, or middle ear to the preseptal space.49

EYELID MARGIN DISEASE

The eyelid margin equivalent of folliculitis is the external hordeolum (stye). It
represents an Staphylococcus aureus infection of the glands of Zeis or Moll at the base of the hair follicle. An
internal hordeolum is an acute infection involving the meibomian
glands. An acute hordeolum can progress to a perifolliculitis, which
resembles a furuncle, a cutaneous abscess centered around a solitary
follicle with associated pain and induration and a shiny, bright red area. Spontaneous
drainage may occur. The pathology shows typical changes
of folliculitis with neutrophils and an abscess and variable destruction
of the hair follicle.

Staphylococcal blepharitis is a common cause of anterior eyelid, ocular
surface, and corneal inflammation. The eyelids in staphylococcal blepharitis
are inflamed with moderate erythema and edema, and there are hard, brittle, fibrinous
scales at the base of the lashes. Collarettes
are formed by fibrin exudation of the ulcerated skin at the base of the
lash. Poliosis (white lashes), madarosis (loss of lashes), tylosis (irregularity
of the lid margin), and broken and misdirected lashes may
be present and are related to damage to the hair follicles. External
and internal hordeolums are seen as an extension of the staphylococcal
infection.

The normal eyelids are colonized by Staphylococcus aureus and Staphylococcus epidermidis approximately 10% and 95% of the time, respectively. In patients with
staphylococcal disease, Staphylococcus aureus has been isolated approximately 47% of the time, with Staphylococcus epidermidis, Propionibacterium acnes, and Corynebacterium species present in higher than normal quantities.50,51 Others have reported similar quantitative cultures and biotypes of Staphylococcus epidermidis in patients with and without blepharitis.52 No consistent difference is evident in the strains of these organisms
to explain the clinical condition. Colonization of the lids with Staphylococcus aureus occurs intermittently in the normal host but is excessive in the atopic
patient and in patients with acute folliculitis. The lid inflammatory
reaction in chronic staphylococcal blepharitis may be related to a combination
of factors, including actual infection and other variables, such
as toxins,53 lipases (splitting meibomian triglycerides to toxic fatty acids),54 and delayed-type hypersensitivity.55

Filtrates prepared from patients with staphylococcal blepharitis caused
by Staphylococcus aureus and Staphylococcus epidermidis have produced toxigenic conjunctivitis in normal eyes.38 There are several candidates for this response, including exfoliative
toxin, toxic shock syndrome toxin, and the beta, gamma, and delta toxins
or the lipases. The lipases are sterol and fatty wax esters that may
alter the viscosity and surface tension of the tear film and ocular
flora.56 Some investigators have not found the staphylococcal toxins to be significant
factors in causing blepharitis.53 Enhanced cell-mediated immunity to Staphylococcus aureus has been found in 40% of patients with chronic blepharitis,57,58 although in an animal model immunity to Staphylococcus aureus is an absolute necessity for the production of ulcerative blepharitis, phlyctenules, and
marginal infiltrates.55,59,60 This animal model suggests that the eyelid and corneal lesions represent
a hypersensitivity response rather than a direct bacterial infection. The
cell wall of Staphylococcus aureus consists of three major components: peptidoglycan, protein A, and ribitol
teichoic acid. Studies by Mondino55 suggest that hypersensitivity to ribitol teichoic acid, the major antigenic
determinant of Staphylococcus aureus, is important in the immunopathogenesis of blepharitis and corneal lesions
in the rabbit model. Correspondingly, the antibody response to ribitol
teichoic acid may be the only serologic test of clinical importance
in the diagnosis of systemic staphylococcal diseases7,8,61 and possibly chronic blepharitis. Giese and colleagues further evaluated
the effect of Staphylococcus aureus phage lysate vaccination in the rabbit animal model but was unable to
find a beneficial effect,61 despite finding enhanced antibody response to ribitol teichoic acid. This
form of vaccination has produced minor improvement in some patients
with furunculosis, pustular acne, pyoderma, eczema, bronchial asthma, upper
respiratory infections, and staphylococcal enterocolitis.61

Infectious eczematoid dermatitis is an immune skin reaction occurring in
middle-aged women that is related to staphylococcal or streptococcal
blepharitis. It is often bilateral, with the entire upper lid involved
with vesiculation, pustulation, crusting, and lichenification. Staphylococcal
or streptococcal antigens act as haptens.

Angular blepharitis is associated with fissuring, scaling, maceration, lichenification, or
erythema of the lateral or medial canthal area. There
may be conjunctival hyperemia and follicular conjunctivitis.62 Phlyctenular keratitis, marginal catarrhal infiltrates, and corneal ulcers
characteristic of staphylococcal blepharitis can occur. The disease
is most common in adolescents in warm climates and can be recurrent. Moraxella lacunata is the main pathogen in warm environments, but Staphylococcus aureus may be more common in colder climates.63 Dysgonic fermenter-2 bacterium has also been isolated.64

Eyelid edema can be quite marked in association with acute catarrhal conjunctivitis
from streptococcal infection but rarely progresses to gangrene.

CONJUNCTIVAL DISEASE

Ophthalmia neonatorum is an acute catarrhal (inflammatory) conjunctivitis
of newborns with moderate mucopurulent discharge or a subacute conjunctivitis
with a mild mucoid discharge. It is usually acquired in the
newborn nursery but may be a harbinger or focus of systemic infection. Staphylococcal
or streptococcal conjunctivitis can have a very acute
purulent onset in neonates and can appear similar to gonococcal conjunctivitis.

Most cases of bacterial conjunctivitis in children are caused by gram-positive
cocci (aerobic or anaerobic),65 with Staphylococcus aureus being the most frequent cause of either acute or chronic bacterial conjunctivitis. Staphylococcal conjunctivitis in children presents acutely
with scanty discharge and lower palpebral conjunctival involvement. Catarrhal
conjunctivitis in adolescents and adults may occur as an acute
conjunctival infection associated with redness, discharge, and foreign-body
sensation caused by staphylococcal infection with or without
associated blepharitis. The discharge is usually mild and mucoid with
a mild papillary hypertrophy. Acute conjunctivitis can cause an acute
purulent conjunctivitis from the elaboration of exotoxins and biologically
active substances such as hemolysin, fibrinolysin, and coagulase, which
produces a mucopurulent discharge and stickiness of the lids upon
awakening. Staphylococcus epidermidis is an infrequent cause of conjunctivitis. A seasonal variation may be
seen. Staphylococcal conjunctivitis in adults is occasionally chronic
secondary to blepharitis with prominent involvement of the tarsal portion
of the conjunctiva.

Epidemics of acute purulent pneumococcal conjunctivitis have been described, usually
in the colder months in northern climates. It has a predilection
for children and causes a moderately severe mucopurulent exudation
and chemosis. Subconjunctival hemorrhages are often seen and usually
involve the upper tarsal conjunctiva or fornix. Purulent conjunctivitis
with other streptococci and staphylococci is not uncommon. Streptococcal
conjunctivitis occasionally has a pseudomembrane or true membrane
formation. The latter is characterized by a coagulative fibrinous
exudate penetrating the epithelial and subepithelial tissues, especially
involving the bulbar conjunctiva. Streptococcus pyogenes may present with an acute purulent conjunctivitis with chemosis and occasionally
membranes or pseudomembranes. Scarlet fever may provoke an
associated toxic conjunctivitis, and streptococcal impetigo can spread
from the skin of the lids.

Chronic conjunctivitis is most commonly caused by Staphylococcus aureus with an associated blepharitis. The conjunctival inflammation may be the
result of direct infection or the release of toxins, similar to the
mechanism of marginal keratitis. Conjunctival findings in chronic staphylococcal
blepharitis (chronic catarrhal conjunctivitis) include mild
hyperemia and a chronic papillary conjunctival reaction with minimal
cellular infiltration. Chronic streptococcal or staphylococcal conjunctivitis
can also be seen in association with chronic dacryocystitis.

Angular conjunctivitis is seen in association with medial or lateral angular
blepharitis and has findings similar to those of acute or chronic
catarrhal conjunctivitis.

Staphylococcal blepharitis produces a toxic punctate epithelial keratitis, especially
of the inferior cornea. These lesions are fine, medium-sized, or
blotchy and stain with fluorescein. Catarrhal corneal infiltrates
of Staphylococcus are commonly seen at the 2, 4, 8, and 10 o'clock meridians of the peripheral
cornea where there is eyelid margin contact with the cornea causing
this immunologic response to staphylococcal antigens. These infiltrates
are arc-shaped and are located 1 or 2 mm inside the limbus.

Phlyctenulosis, which is a cell-mediated hypersensitivity response to staphylococcal
antigen, can occur at the limbus, cornea, or conjunctiva. It
begins as a white or yellow superficial infiltrate that ulcerates
and heals in approximately 2 weeks. The limbal phlyctenule often straddles
the limbus but may occur in the cornea or conjunctiva alone. Scarring
can occur and the inflammation can attract a leash of superficial
blood vessels.

In one study, the frequency of staphylococcal marginal keratitis was the
same in patients with or without enhanced cell-mediated immunity to Staphylococcus aureus protein A.52 Patients with marginal keratitis requiring treatment with steroids, however, were
more likely to have enhancement.52 The cell walls of coagulase-negative staphylococci do not contain protein
A. The present understanding of the pathogenesis of marginal keratitis
is that it is caused by the expression of a cell-mediated immune
response at the limbus to Staphylococcus aureus on the eyelids in patients with a prior systemic enhancement of cell-mediated
immunity. This may indicate a possible role for selective desensitization. There
are many unanswered questions about staphylococcal
blepharitis; features of the disease are partially but not completely
explained by toxins, cell wall antigenicity, cellular and humoral immunity, and
host susceptibility.

Risk factors for suppurative bacterial corneal infections include contact
lens wear, trauma, and corneal compromise. Staphylococcus aureus is one of the most common causative organisms in bacterial keratitis in
the northern and northeastern United States and Canada, both in normal
hosts and in immunocompromised corneas. It has a tendency for central
corneal location with a hypopyon and occasionally a perforation. The
keratitis is yellow-white with a well-demarcated stromal infiltrate
located directly below the epithelial defect. Multiple, small, superficial
satellite stromal infiltrates can develop. Posterior corneal abscesses
can occur, leading to perforation. Occasionally, a staphylococcal
ulcer is indolent, with only mild anterior chamber reaction and no hypopyon.

Corneal complications from streptococcal infection include a suppurative
keratitis and a marginal keratitis. The suppurative keratitis of Streptococcus pneumoniae is a common cause of central corneal ulcers, and a presumptive diagnosis
can be made from the serpiginous appearance of the ulcer. At the onset, the
corneal epithelium becomes lusterless and hazy as the stroma
becomes infiltrated. The corneal epithelium breaks down to form an ulcer, which
spreads centrally with the leading edge undermined as the peripheral
edge becomes sloping from healing. The cornea can rapidly become
necrotic. Other streptococcal ulcers are characterized by infiltration, necrosis, and
epithelial ulceration, with hypopyon uncommon but
with no other distinguishing features. Occasionally a marginal ulcer develops
in association with a streptococcal conjunctivitis or with erysipelas
of the face.

Infectious crystalline keratopathy is commonly caused by α-hemolytic
streptococci or nutritionally variant streptococci, among other organisms. These
organisms may secrete an intrastromal glycocalyx or slime
layer, which renders them relatively impervious to antimicrobials. The
infection is indolent with minimal signs of inflammation and is difficult
to eradicate. The infiltrates have the appearance of fine spicules
or snowflakes in the anterior stroma. The overlying corneal epithelium
is usually intact. The crystalline appearance may be related to the
production of dextran by the organism or to the formation of a bacterial
biofilm. The organisms involved in this infection are characteristically
slow growing or have an inability to grow on culture media.

SCLERAL DISEASE

Bacterial scleritis is usually the result of scleral extension of primary
corneal infections. Staphylococcal blepharitis can be associated with
a painful, tender nodule in the sclera that may persist for several
weeks. Primary bacterial scleritis with or without keratitis may occur
and may follow accidental or surgical injury or a severe endophthalmitis. Less
frequently, a scleral abscess is related to a metastatic staphylococcal
or pneumococcal infection or is associated with an implanted
retinal buckle. Posterior scleral staphylococcal or pneumococcal infection
is rare but can produce exophthalmos, pain on ocular rotation, vitreitis, or
iridocyclitis. Panophthalmitis, ocular perforation, or
phthisis bulbi may ensue.

LACRIMAL DISEASE

Lacrimal gland infections (dacryoadenitis) caused by gram-positive organisms
can occur from metastatic spread, from penetrating injuries, from
surrounding infections of the skin, teeth, or sinuses, or from middle
ear infections.

Dacryocystitis is a common complication of nasolacrimal duct obstruction
in the elderly. Organisms include Staphylococcus and Streptococcus.

PRESEPTAL AND ORBITAL DISEASE

Orbital cellulitis is a spread of bacteria beyond the septum into the orbit
and is characterized by significant symptoms. There may be headache, fever, lid
edema, rhinorrhea, tenderness to palpation, proptosis, resistance
to retropulsion of the globe, limitation of ocular motility, conjunctival
hyperemia, and chemosis. Compression of the optic nerve
can lead to vascular compromise, and posterior extension can lead to
cavernous sinus thrombosis, subdural empyema, and intracranial abscess
or cellulitis with loss of vision, sepsis, or death. Orbital cellulitis
can occur after penetrating trauma, surgery, neonatal conjunctivitis, panophthalmitis, dacryocystitis, or bacteremia, or from direct extension
of bacterial sinusitis. Although the most common organisms in adults
are Staphylococcus aureus and Streptococcus pyogenes, the most common pathogen in children is H. influenzae; the latter may lead to bacteremia, metastatic infection, and meningitis.67 In childhood orbital cellulitis, conjunctival culture, blood culture, and
needle aspiration may be necessary to confirm the organism. Adults
are more likely to have a portal of entry to culture but may require
needle aspiration to confirm.

ENDOPHTHALMITIS

Staphylococcal endophthalmitis after trauma or intraocular surgery is caused
by Staphylococcus aureus and Staphylococcus epidermidis. Both organisms can also cause panophthalmitis. Approximately 60% to 70% of
postsurgical endophthalmitis cases are caused by Staphylococcus epidermidis (or other related coagulase-negative staphylococci). These strains do
not typically express toxins, and components of their cell walls are only
mildly inflammatory. Staphylococcus epidermidis endophthalmitis usually begins insidiously and progresses more slowly
than does Staphylococcus aureus endophthalmitis.

The frequency of endophthalmitis may relate to the propensity of Staphylococcus epidermidis to adhere to medical devices, including intraocular implants. The organisms
involved in endophthalmitis usually originate from the skin or conjunctival
flora, as demonstrated by phage and DNA typing. Streptococcus pneumoniae or other streptococci cause an endophthalmitis in association with intraocular
surgery or penetrating injury, especially in the presence of
chronic pneumococcal dacryocystitis. Approximately 25% of endophthalmitis
cases are caused by Staphylococcus aureus, Streptococcus pneumoniae, viridans streptococci, or Enterococcus. The remaining are caused by P. aeruginosa or Bacillus cereus. Experimental staphylococcal endophthalmitis is commonly studied. Most
studies use 30 to 2000 Staphylococcus aureus organisms injected into the rabbit vitreous, with clinical infection noted
within 24 to 48 hours. Streptococci are associated with the endophthalmitis
that is seen in association with filtering conjunctival blebs. Streptococci
are especially destructive within the eye, causing rapid
retinal damage from enzyme activity and a poor visual result.

Endogenous endophthalmitis can arise from cutaneous infections, endocarditis, tonsillitis, otitis
media, sinusitis, or osteomyelitis; in some
instances it comes from unknown sources.

Post-traumatic endophthalmitis is characterized by a mix of organisms related
to the contamination introduced. Bacillus species are the most devastating. Gram-positive cocci are occasionally
present.

A sterile endophthalmitis (uveitis) can be seen in association with some
gram-positive infections (especially Streptococcus), possibly as a result of toxins diffusing locally or from a distant infection
site. Acute posterior multifocal placoid pigment epitheliopathy
may be an immunologically mediated vascular disease associated with
several causes, including group A streptococcal infection.68